{"id":"https://openalex.org/W4200027262","doi":"https://doi.org/10.1021/acs.jcim.1c01180","title":"Exploring the pH- and Ligand-Dependent Flap Dynamics of Malarial Plasmepsin II","display_name":"Exploring the pH- and Ligand-Dependent Flap Dynamics of Malarial Plasmepsin II","publication_year":2021,"publication_date":"2021-12-29","ids":{"openalex":"https://openalex.org/W4200027262","doi":"https://doi.org/10.1021/acs.jcim.1c01180","pmid":"https://pubmed.ncbi.nlm.nih.gov/34964641"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.1c01180","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.1c01180","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8812262","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5075279030","display_name":"Jack A. Henderson","orcid":"https://orcid.org/0000-0001-6675-7944"},"institutions":[{"id":"https://openalex.org/I126744593","display_name":"University of Maryland, Baltimore","ror":"https://ror.org/04rq5mt64","country_code":"US","type":"education","lineage":["https://openalex.org/I126744593"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jack A. Henderson","raw_affiliation_strings":["Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States"],"raw_orcid":"https://orcid.org/0000-0001-6675-7944","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States","institution_ids":["https://openalex.org/I126744593"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5084434392","display_name":"Jana Shen","orcid":"https://orcid.org/0000-0002-3234-0769"},"institutions":[{"id":"https://openalex.org/I126744593","display_name":"University of Maryland, Baltimore","ror":"https://ror.org/04rq5mt64","country_code":"US","type":"education","lineage":["https://openalex.org/I126744593"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jana Shen","raw_affiliation_strings":["Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States"],"raw_orcid":"https://orcid.org/0000-0002-3234-0769","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States","institution_ids":["https://openalex.org/I126744593"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5084434392"],"corresponding_institution_ids":["https://openalex.org/I126744593"],"apc_list":null,"apc_paid":null,"fwci":1.7778,"has_fulltext":false,"cited_by_count":11,"citation_normalized_percentile":{"value":0.85403852,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":91,"max":99},"biblio":{"volume":"62","issue":"1","first_page":"150","last_page":"158"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10091","display_name":"Malaria Research and Control","score":0.9977999925613403,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10091","display_name":"Malaria Research and Control","score":0.9977999925613403,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9976999759674072,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10407","display_name":"Lipid Membrane Structure and Behavior","score":0.994700014591217,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.6146779656410217},{"id":"https://openalex.org/keywords/ligand","display_name":"Ligand (biochemistry)","score":0.6032091379165649},{"id":"https://openalex.org/keywords/protonation","display_name":"Protonation","score":0.6004670858383179},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5689713358879089},{"id":"https://openalex.org/keywords/pepstatin","display_name":"Pepstatin","score":0.5157866477966309},{"id":"https://openalex.org/keywords/substrate","display_name":"Substrate (aquarium)","score":0.5042730569839478},{"id":"https://openalex.org/keywords/stereochemistry","display_name":"Stereochemistry","score":0.4662574529647827},{"id":"https://openalex.org/keywords/combinatorial-chemistry","display_name":"Combinatorial chemistry","score":0.44201144576072693},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.2861889600753784},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.2618272006511688},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.17392364144325256},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.13520598411560059},{"id":"https://openalex.org/keywords/receptor","display_name":"Receptor","score":0.10973414778709412},{"id":"https://openalex.org/keywords/organic-chemistry","display_name":"Organic chemistry","score":0.10692644119262695}],"concepts":[{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.6146779656410217},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.6032091379165649},{"id":"https://openalex.org/C30095370","wikidata":"https://www.wikidata.org/wiki/Q899488","display_name":"Protonation","level":3,"score":0.6004670858383179},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5689713358879089},{"id":"https://openalex.org/C2776350231","wikidata":"https://www.wikidata.org/wiki/Q7166509","display_name":"Pepstatin","level":4,"score":0.5157866477966309},{"id":"https://openalex.org/C2777289219","wikidata":"https://www.wikidata.org/wiki/Q7632154","display_name":"Substrate (aquarium)","level":2,"score":0.5042730569839478},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.4662574529647827},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.44201144576072693},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.2861889600753784},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2618272006511688},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.17392364144325256},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.13520598411560059},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.10973414778709412},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.10692644119262695},{"id":"https://openalex.org/C18903297","wikidata":"https://www.wikidata.org/wiki/Q7150","display_name":"Ecology","level":1,"score":0.0},{"id":"https://openalex.org/C2776714187","wikidata":"https://www.wikidata.org/wiki/Q212410","display_name":"Protease","level":3,"score":0.0},{"id":"https://openalex.org/C145148216","wikidata":"https://www.wikidata.org/wiki/Q36496","display_name":"Ion","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006863","descriptor_name":"Hydrogen-Ion Concentration","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006863","descriptor_name":"Hydrogen-Ion Concentration","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006863","descriptor_name":"Hydrogen-Ion Concentration","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008288","descriptor_name":"Malaria","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D008288","descriptor_name":"Malaria","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D008288","descriptor_name":"Malaria","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015800","descriptor_name":"Protozoan Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015800","descriptor_name":"Protozoan Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015800","descriptor_name":"Protozoan Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016282","descriptor_name":"Aspartic Acid Endopeptidases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D016282","descriptor_name":"Aspartic Acid Endopeptidases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D016282","descriptor_name":"Aspartic Acid Endopeptidases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.1c01180","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.1c01180","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:34964641","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34964641","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of chemical information and modeling","raw_type":null},{"id":"pmh:oai:pubmedcentral.nih.gov:8812262","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8812262","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:8812262","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8812262","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.8399999737739563}],"awards":[{"id":"https://openalex.org/G3161687143","display_name":null,"funder_award_id":"R01 GM098818","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G5224315540","display_name":null,"funder_award_id":"R01GM098818","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":45,"referenced_works":["https://openalex.org/W1552369200","https://openalex.org/W1581608952","https://openalex.org/W1971679196","https://openalex.org/W1974030600","https://openalex.org/W1977496028","https://openalex.org/W1988803526","https://openalex.org/W1997772366","https://openalex.org/W2003312854","https://openalex.org/W2004145462","https://openalex.org/W2014004271","https://openalex.org/W2016868425","https://openalex.org/W2027408247","https://openalex.org/W2031796366","https://openalex.org/W2032187756","https://openalex.org/W2035687084","https://openalex.org/W2037288608","https://openalex.org/W2048833096","https://openalex.org/W2060433756","https://openalex.org/W2067471686","https://openalex.org/W2071582487","https://openalex.org/W2073963375","https://openalex.org/W2076407822","https://openalex.org/W2080800689","https://openalex.org/W2083219790","https://openalex.org/W2102376488","https://openalex.org/W2106140689","https://openalex.org/W2120715487","https://openalex.org/W2132262459","https://openalex.org/W2144764119","https://openalex.org/W2164231548","https://openalex.org/W2256313030","https://openalex.org/W2283762586","https://openalex.org/W2327581403","https://openalex.org/W2330799739","https://openalex.org/W2411825743","https://openalex.org/W2604909312","https://openalex.org/W2758005129","https://openalex.org/W2788212154","https://openalex.org/W2890361239","https://openalex.org/W2901677424","https://openalex.org/W2944211377","https://openalex.org/W3082580455","https://openalex.org/W3114872620","https://openalex.org/W4207078658","https://openalex.org/W4211114880"],"related_works":["https://openalex.org/W2058621883","https://openalex.org/W2015565196","https://openalex.org/W2411404836","https://openalex.org/W2343939489","https://openalex.org/W2104504271","https://openalex.org/W2080415597","https://openalex.org/W1985364989","https://openalex.org/W2114661152","https://openalex.org/W1866017395","https://openalex.org/W2036503064"],"abstract_inverted_index":{"Malaria":[0],"remains":[1],"a":[2,29,63,156],"global":[3],"health":[4],"threat\u2500over":[5],"400,000":[6],"deaths":[7],"occurred":[8],"in":[9,79,91],"2019.":[10],"Plasmepsins":[11],"are":[12,76,138],"promising":[13],"targets":[14],"of":[15,32,39,53,115,132,159,164,168],"antimalarial":[16],"therapeutics;":[17],"however,":[18,117],"no":[19],"inhibitors":[20],"have":[21],"reached":[22],"the":[23,27,33,46,54,70,80,85,89,96,101,108,121,129,143,153,165],"clinic.":[24],"To":[25],"fuel":[26],"progress,":[28],"detailed":[30],"understanding":[31],"pH-":[34,160],"and":[35,58,74,83,99,135,140,148,161,175],"ligand-dependent":[36],"conformational":[37],"dynamics":[38,51,163],"plasmepsins":[40,169],"is":[41],"needed.":[42],"Here":[43],"we":[44],"present":[45],"continuous":[47],"constant":[48],"pH":[49],"molecular":[50],"study":[52,151],"prototypical":[55],"plasmepsin":[56],"II":[57],"its":[59],"complexed":[60],"form":[61],"with":[62,142],"substrate":[64],"analogue.":[65],"The":[66,104],"simulations":[67,105],"revealed":[68],"that":[69,84,107],"catalytic":[71],"dyads":[72],"D34":[73,95],"D214":[75,100],"highly":[77],"coupled":[78],"apo":[81],"protein":[82],"pepstatin":[86,119],"binding":[87,120],"enhances":[88],"difference":[90],"proton":[92],"affinity,":[93],"making":[94],"general":[97,102],"base":[98],"acid.":[103],"showed":[106],"flap":[109,122],"adopts":[110],"an":[111],"open":[112,126],"state":[113,131],"regardless":[114],"pH;":[116],"upon":[118],"can":[123],"close":[124],"or":[125],"depending":[127],"on":[128],"protonation":[130],"D214.":[133],"These":[134],"other":[136],"data":[137],"discussed":[139],"compared":[141],"off-targets":[144],"human":[145],"cathepsin":[146],"D":[147],"renin.":[149],"This":[150],"lays":[152],"groundwork":[154],"for":[155],"systematic":[157],"investigation":[158],"ligand-modulated":[162],"entire":[166],"family":[167],"to":[170],"help":[171],"design":[172],"more":[173],"potent":[174],"selective":[176],"inhibitors.":[177]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":7}],"updated_date":"2026-06-24T13:16:06.693445","created_date":"2025-10-10T00:00:00"}
